Research Interests:

Our laboratory is interested in the intracellular effector mechanisms that couple specific receptor-ligand interactions with opening of the endothelial paracellular pathway. More specifically, we have focused on the tyrosine phosphorylation signaling events that regulate protein-protein interactions within the zonula adherens multiprotein complex, actin organization, and cell-cell homophilic adhesion. Our studies have included bacterial constituents (e.g. lipopolysaccharide or endotoxin) cytokines (e.g. TNF-alpha), and members of a family of novel counteradhesive proteins (e.g. thrombospondin-1 and SPARC i.e. Secreted Protein Acidic and Rich in Cysteine). More recently, we have begun to study a receptor protein tyrosine phosphatase (PTP), PTPmu, that associates with and restrains tyrosine phosphorylation of zonula adherens proteins. More recently, we have studied the ability of EGF motif-containing proteins like thrombospondins, to activate the epidermal growth factor receptor (EGFR) and the role this plays in epithelial repair.

In a collaborative project with the laboratory of Dr. Alan S. Cross, we are engaged in studies of endogenous sialidases and the role of desialylation of surface structures on neutrophils and the endothelial barrier and how these events regulate neutrophil adherence to and migration across the endothelium. In another collaboration, we are studying the signaling events that couple stimulation by either the prokaryotic protein, zonula occludin toxin (ZOT), or the eukaryotic homologue, zonulin (now identified as prehaptoglobin-2), with tight junction disassembly.